Trifluoroacetic acid → (S)-3-(3-(4-(1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one

HRID 539018Notes

Reaction equation

HRID 539018 reaction equation
[Si](OCCN1[CH2:15][C@H:14]([CH:16]([CH3:18])[CH3:17])[N:13]([C:19]2[CH:24]=[CH:23][N:22]3[N:25]=[CH:26][C:27]([C:28]4[CH:33]=[CH:32][C:31]([C:34]5[N:35](COCC[Si](C)(C)C)[CH:36]=[CH:37][N:38]=5)=[CH:30][CH:29]=4)=[C:21]3[N:20]=2)[C:12]1=[O:47])(C(C)(C)C)(C)C.FC(F)(F)C(O)=[O:51]>ClCCl>[NH:35]1[CH:36]=[CH:37][N:38]=[C:34]1[C:31]1[CH:32]=[CH:33][C:28]([C:27]2[CH:26]=[N:25][N:22]3[CH:23]=[CH:24][C:19]([N:13]4[C@@H:14]([CH:16]([CH3:18])[CH3:17])[CH2:15][O:47][C:12]4=[O:51])=[N:20][C:21]=23)=[CH:29][CH:30]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67034424(S)-1-(2-(tert-butyldimethylsilyloxy)ethyl)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)imidazolidin-2-one

Product 1

HCID 50997719(S)-3-(3-(4-(1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-oneYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-1-(2-(tert-butyldimethylsilyloxy)ethyl)-4-isopropyl-3-(3-(4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)imidazolidin-2-one (15 mg, 0.022 mmol) in dichloromethane (0.3 mL) and trifluoroacetic acid (0.3 mL) was stirred at ambient temperature for 24 hours. The solvents were evaporated, and the residue was taken up in MeOH. A few drops of 1N LiOH solution was added. The mixture was stirred for 10 minutes. The reaction mixture was diluted with water and extracted with dichloromethane. The combined organic layers were washed with brine, dried and concentrated. The residue was purified by column chromatography (12% MeOH in dichloromethane) to give (S)-3-(3-(4-(1H-imidazol-2-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one (5 mg, 52%) as a pale yellow solid. 1H NMR (400 MHz, CD3OD) δ 8.66 (d, J=7.6 Hz, 1H), 8.47 (s, 1H), 8.18 (d, J=8.4 Hz, 2H), 8.13 (d, J=8.0 Hz, 1H), 7.90 (d, J=8.4 Hz, 2H), 7.16 (s, 2H), 3.2-3.8 (m, 7H), 2.91 (m, 1H), 1.12 (d, 3H), 0.89 (d, 3H). LCMS (APCI+) m/z 432.3 [M+H]

Workup

  1. customThe solvents were evaporated
  2. additionA few drops of 1N LiOH solution was added
  3. additionThe reaction mixture was diluted with water
  4. extractionextracted with dichloromethane
  5. washThe combined organic layers were washed with brine
  6. customdried
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (12% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-669438e3e4e64e098d6eeba6e44feaf0
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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